Shinmura K, Kohno T, Takahashi M, Sasaki A, Ochiai A, Guilford P, Hunter A, Reeve A E, Sugimura H, Yamaguchi N, Yokota J
Biology Division, Pathology Division and Cancer Information and Epidemiology Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Carcinogenesis. 1999 Jun;20(6):1127-31. doi: 10.1093/carcin/20.6.1127.
Gastric cancer frequently occurs in family members with hereditary non-polyposis colorectal cancer (HNPCC) and Li-Fraumeni syndrome (LFS) and germline E-cadherin mutations were recently identified in a subset of familial gastric cancers. Thus, families with an aggregation of gastric cancers were recruited by reviewing the genealogical trees of 3632 patients with gastric cancer. The criteria for recruiting such families were the following: at least three relatives should have gastric cancer and one of them should be a first degree relative of the other two; at least two successive generations should be affected; in one of the relatives gastric cancer should be diagnosed before age 50. Thirty-one cases (0.9%) fitted all three of these criteria. There were only gastric cancer patients in 18 of the 31 families and there were no families that fitted clinical criteria of HNPCC or LFS. Paraffin-embedded tissues were available in 29 probands and DNA was successfully isolated for molecular analyses in 13 probands. RER phenotype was detected in three (23%) cases, whereas germline p53 mutations were detected in none of 13 cases. A germline E-cadherin mutation was detected in one of three diffuse types and none of 10 intestinal types, however, a mutation resulting in the replacement of Gly by Val was detected in the precursor sequence. Thus, although familial clustering of gastric cancer occurs in approximately 1% of gastric cancer patients, germline mutations of the DNA mismatch repair, p53 and E-cadherin genes do not significantly contribute to such a clustering.
胃癌常见于患有遗传性非息肉病性结直肠癌（HNPCC）和李-佛美尼综合征（LFS）的家庭成员中，并且最近在一部分家族性胃癌中发现了种系E-钙黏蛋白突变。因此，通过查阅3632例胃癌患者的族谱，招募了胃癌聚集性家族。招募此类家族的标准如下：至少三名亲属患有胃癌，其中一人应为另外两人的一级亲属；至少两代人受到影响；其中一名亲属的胃癌应在50岁之前确诊。31例（0.9%）符合所有这三条标准。31个家族中有18个家族只有胃癌患者，没有家族符合HNPCC或LFS的临床标准。29名先证者有石蜡包埋组织，13名先证者成功分离出DNA用于分子分析。13例中3例（23%）检测到RER表型，而13例中均未检测到种系p53突变。在3例弥漫型中的1例检测到种系E-钙黏蛋白突变，10例肠型中均未检测到，但在前体序列中检测到一个导致甘氨酸被缬氨酸取代的突变。因此，虽然约1%的胃癌患者存在胃癌家族聚集现象，但DNA错配修复、p53和E-钙黏蛋白基因的种系突变对这种聚集现象没有显著影响。
